FERRITIN-GUIDED THERAPEUTIC PLASMA EXCHANGE (TPE) ADMINISTRATION IN COVID-19-INDUCED CYTOKINE STORM SYNDROME: A CASE SERIES

ABSTRACT

SESSION TITLE Management of COVID-19-Induced Complications SESSION TYPE Rapid Fire Case Reports PRESENTED ON 10/19/2022 1245 pm - 145 pm INTRODUCTION: Therapeutic plasma exchange (TPE) in the management of COVID-19-induced cytokine storm syndrome (CSS) has remained unclear since the pandemic's emergence. A recent meta-analysis by Beraud et. al examined the use of TPE for treatment of CSS in COVID-19 patients. Although inconsistencies were noted, they demonstrated a general downtrend in cytokine markers and acute phase reactants following TPE administration. TPE was associated with improvements in clinical outcomes and appeared safe in critically ill patients. The analysis highlighted an ongoing need to establish clear criteria to identify a target population. This case series presents 3 critically ill adult COVID-19 patients with CSS and extreme hyperferritinemia (>10,000 ng/mL) who received TPE. We propose the use of ferritin as a sole biomarker for guiding therapy in this patient demographic. CASE PRESENTATION Patient 1 presented with ferritin 16,060 and CRP 8.22. Despite receiving standard COVID-19 therapies, she decompensated and required intubation. Repeat labs revealed ferritin 92,488 and CRP 9.75. TPE was initiated. Ferritin decreased following each TPE session as shown in Graph 1. Patients 2 and 3 also presented with extreme hyperferritinemia and showed a similar downtrend following TPE therapy. All 3 patients made successful recoveries. DISCUSSION: Hyperferritinemia is present across a range of inflammation-mediated disorders and considered a validated biomarker in various disease states, including COVID-19. There are many hypothesized mechanisms of elevated ferritin in COVID-19;one of which is cytokine release. Severe-to-critical COVID-19 patients have shown higher ferritin levels compared to mild-to-moderately ill patients, and non-survivors have shown higher levels than survivors. Unlike those reported by Beraud et. al, our patients presented with extreme hyperferritinemia. All 3 showed a consistent downtrend in ferritin after TPE sessions, and resolution or near-resolution of hyperferritinemia. CRP levels were also obtained, however 2 of 3 cases showed only mild elevation, and levels trended inconsistently after individual sessions. As such, it was not used to gauge treatment duration or efficacy. CONCLUSIONS: Since biomarker selection and thresholds for therapy remain unclear, we propose further investigation into a ferritin-guided approach to TPE therapy in critically ill COVID-19 patients with CSS. Additionally, the marked ferritin elevation seen in extreme hyperferritinemia may aid in establishing upper thresholds above which TPE would no longer be considered safe or effective. Lastly, given that previous studies showed clinical improvements in patients with mild-to-moderate elevation, we consider that the rate of and/or percentage change in ferritin level may yield a reliable algorithm to direct therapy. Establishing selection criteria in this patient population may prove critical for reducing morbidity and mortality. Reference #1 Beraud, M., Hashami, S. A., Lozano, M., Bah, A., & Keith, P. (2022). Role of therapeutic plasma exchange in the management of COVID-19-induced cytokine storm syndrome. Transfus Apher Sci, 103433. https//doi.org/10.1016/j.transci.2022.103433 Reference #2 Kaushal, K., Kaur, H., Sarma, P., Bhattacharyya, A., Sharma, D. J., Prajapat, M., Pathak, M., Kothari, A., Kumar, S., Rana, S., Kaur, M., Prakash, A., Mirza, A. A., Panda, P. K., Vivekanandan, S., Omar, B. J., Medhi, B., & Naithani, M. (2022). Serum ferritin as a predictive biomarker in COVID-19. A systematic review, meta-analysis and meta-regression analysis. J Crit Care, 67, 172-181. https//doi.org/10.1016/j.jcrc.2021.09.023 Reference #3 Krzych, L. J., Putowski, Z., Czok, M., & Hofman, M. (2021). What Is the Role of Therapeutic Plasma Exchange as an Adjunctive Treatment in Severe COVID-19 A Systematic Review. Viruses, 13(8). https//doi.org/10.3390/v13081484 DISCLOSURES No relevant relationships by Stefani Delvecchio No relevant relationships by Sean Masi No relevant relationships by Chris Recker-Herman